The present invention is directed to antibacterial 5R,6S-6-(1R-hydroxyethyl)-2-(3-thiolanyl)thio-2-carbapenem-3-carboxylic acids, as depicted by the for below; the pharmaceutically-acceptable salts and in vivo hydrolyzable esters thereof; and intermediates useful in the preparation of said compounds.
There are numerous reports in the literature concerning antibacterial 2-(alkylthio)-2-carbapenems and related compounds. See, for example, Andrus et al , J. Am. Chem. Soc., vol. 106, pp. 1808-1811, 1984; Afonso et al., ibid., vol. 104, pp. 6139-6140, 1982; DiNinno et al., Tetrahedron Letters, vol. 23, pp. 3535-3538 (1982); Ganguly et al., J. Antimicrobial Chemotherapy, vol. 9, suppl. C, pp. 1-5 (1982); Ghosez et al., Tetrahedron, vol. 39, pp. 2493-2503, 1983; Girijavallabhan et al., J. Antibiotics, vol. 39, pp. 1182-1190, 1986; Girijavallabhan et al., Tetrahedron Letters, vol. 24, pp. 3179-3182, 1979; Leanza et al., Tetrahedron, vol. 39, pp. 2505-2513, 1983; and Shih et al., Heterocycles, vol. 21, pp. 29-40, 1984.
In addition, antibacterial 5R, 6S-6-(1R-hydroxyethyl)-2-(cis-1-oxo-3-thiolanylthio)-2-penem-3-carboxylic acid and 5R,6S-6-(1R-hydroxyethyl)-2-(1,1-dioxo-3thiolanylthio)-2-penem-3-carboxyli c acid have been disclosed by Hamanaka, U.S. Pat. No. 4,619,924. More recently, the preferred diastereoisomer, 5R,6S-6-(1R-hydroxyethyl)-2-(1R-oxo-3S-thiolanylthio)-2-penem-3-acid, was identified by Volkmann in International Application No. PCT/US87/01114, designating inter alia the United States of America, published on Nov. 17, 1988 as WO-88/08845.